Genetic Variant SOS2:c.*50T>A (chr14-50118294-A-T) – ACMG Classification: Benign (-18 pts)

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_006939.4(SOS2):c.*50T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,469,722 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 35 hom. )

Consequence

SOS2
NM_006939.4 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.63

Variant links:

Genes affected

SOS2 (HGNC:11188): (SOS Ras/Rho guanine nucleotide exchange factor 2) This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]

SOS2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 14-50118294-A-T is Benign according to our data. Variant chr14-50118294-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1202548.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.00428 (5636/1317370) while in subpopulation SAS AF= 0.0169 (1159/68692). AF 95% confidence interval is 0.0161. There are 35 homozygotes in gnomad4_exome. There are 3027 alleles in male gnomad4_exome subpopulation. Median coverage is 19. This position pass quality control queck.

BS2

High AC in GnomAd4 at 502 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOS2	NM_006939.4 link	c.*50T>A		3_prime_UTR_variant	Exon 23 of 23	ENST00000216373.10	NP_008870.2	Q07890-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOS2	ENST00000216373 link	c.*50T>A		3_prime_UTR_variant	Exon 23 of 23	1	NM_006939.4	ENSP00000216373.5		Q07890-1
SOS2	ENST00000543680.5 link	c.*50T>A		downstream_gene_variant		1		ENSP00000445328.1		Q07890-2

Frequencies

GnomAD3 genomes

AF:

0.00330

AC:

503

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00951

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0180

Gnomad FIN

AF:

0.00273

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00435

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00404

AC:

745

AN:

184588

Hom.:

AF XY:

0.00453

AC XY:

450

AN XY:

99416

show subpopulations

Gnomad AFR exome

AF:

0.000553

Gnomad AMR exome

AF:

0.00150

Gnomad ASJ exome

AF:

0.00993

Gnomad EAS exome

AF:

0.000128

Gnomad SAS exome

AF:

0.0140

Gnomad FIN exome

AF:

0.00217

Gnomad NFE exome

AF:

0.00404

Gnomad OTH exome

AF:

0.00457

GnomAD4 exome

AF:

0.00428

AC:

5636

AN:

1317370

Hom.:

Cov.:

AF XY:

0.00466

AC XY:

3027

AN XY:

649098

show subpopulations

Gnomad4 AFR exome

AF:

0.000482

Gnomad4 AMR exome

AF:

0.00156

Gnomad4 ASJ exome

AF:

0.00791

Gnomad4 EAS exome

AF:

0.0000260

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.00284

Gnomad4 NFE exome

AF:

0.00372

Gnomad4 OTH exome

AF:

0.00475

GnomAD4 genome

AF:

0.00330

AC:

502

AN:

152352

Hom.:

Cov.:

AF XY:

0.00346

AC XY:

258

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00951

Gnomad4 EAS

AF:

0.000192

Gnomad4 SAS

AF:

0.0180

Gnomad4 FIN

AF:

0.00273

Gnomad4 NFE

AF:

0.00435

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00414

Hom.:

Bravo

AF:

0.00258

Asia WGS

AF:

0.00722

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 17, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

7.0

DANN

Benign

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over